Infection with ectoparasites in humans is common and remains a major health problem in the U.S. and worldwide. The most common ectoparasites include head lice, body lice, pubic lice and scabies. For example, head lice (Pediculus capitis) is a persistent health problem. Six million school children in United States will become infected with head lice annually; that is, one out of every four students in elementary schools (Consumer Reports, February 1998). A total of about ten million people will be infected when all ages are accounted. The incidence of head lice is only slightly improved from the reported incidence in 1940, which was prior to the advent of insecticides and superior knowledge by the medical establishment.
Infestation with head lice in human typically causes itching and lesion of the scalp, as well as swelling of glands in the neck or under the arms. A secondary problem is that many schools have enforced absenteeism if a child has any nits (lice eggs) in their hair (See, e.g., U.S. Pat. No. 6,103,248). Such a “no-nit” policy has negative social implications for the child and the parents. Head lice is becoming a sensitive social issue. Evidence also strongly supports that head lice could be vectors for systemic human infections. For example Rickettsiae and Spirochetes are known to be obtainable from the blood of the host (head lice are blood suckers like mosquitoes); these organisms multiply in the gut of the head lice, and are found in high numbers in their feces (See, e.g., U.S. Pat. No. 6,103,248). Viruses, like the AIDS virus, have been found in the gut and feces of head lice (See, e.g., U.S. Pat. No. 6,103,248).
Body lice are tiny parasitic insects (Pediculus humanus corporis) that can be spread by close contact with infected people or clothing. They feed on human blood, lay eggs and deposit their fecal matter on skin. Infestation with body lice in humans causes intense itching. When body lice are not feeding on blood, they live in the seams and folds of clothing. Pubic lice are parasitic insects found commonly in the genital area, body hair including hair on the legs, armpit, mustache, eyebrows and eyelashes in humans, especially in young children.
Scabies is caused by a tiny mite (called Human Itch mite) that has infested humans for at least 2,500 years. Scabies can barely be seen by the human eyes. Dermatologists estimate that more than 300 million cases of scabies occur worldwide every year. The condition can strike anyone of any race or age, regardless of personal hygiene. Within several weeks, the patient develops an allergic reaction causing severe itching; often intense enough to keep sufferers awake all night.
Home remedies for these ectoparasites are largely ineffective or inconvenient to apply. For example, remedies against head lice include applying petroleum jelly or mayonnaise on the scalp. Unfortunately, these treatments are ineffective. Commercial treatments also include applying an insecticide on the scalp hair. The marketed products (prescription and OTC) include insecticides such as malathion, gamma benzene hexachloride, permethrin, pyrethrin, or piperonyl butoxide.
These pharmaceutically formulated insecticides are universally admixed in a water based composition such as mousse, foam, ointment, shampoo, lotion, and cream rinse. U.S. Pat. No. 5,783,202 describes a mousse formulation and European Patent 125471 describes a foaming pesticide. These two formulations are limited as they break down quickly (e.g., within 2-30 seconds) and risking the exposure of eyes/ears to the toxic insecticide. In addition, the generated air bubbles in these formulations may be bigger than the pores on the cap of the eggs and hence may actually impede the insecticide activity. U.S. Pat. No. 6,524,602 describes the use of N,O-carboxymethyl-chitosan polymer to increase the retention of formulation on skin. The safety of the polymer and how it affects stability of insecticides have not been established.
U.S. Pat. No. 6,103,248 describes a thick ointment preparation containing an insecticide, lipophillic carrier and a surfactant. The carrier has a viscosity within the range of 10,000 centipoise to about 85,000 centipoise at 21° C. A main disadvantage associated with such formulations is the presence of surfactant, which may raise the pH of the formulation thus affecting the stability of insecticides like malathion which is pH sensitive. Because of its high viscosity and oily nature, the formulation is difficult to spread evenly in the hair, and to wash away from the hair (requires a minimum of two washings). Some head lice products are available as shampoo; however the efficacy of such dosage form is uncertain. The shampoo needs to be diluted with water to 1:20 to 1:30 times for application to the hair which lowers the efficacy of the insecticide. Head lice have spiracles, by which the adult lice breathe and the eggs have opercula by which lice larvae in the eggs exchange oxygen. When lice comes in contact with water, it grasps hair reflectively and close their breathing spiracles to avoid being drowned. The opercula in eggs also close when in contact with water thus making it difficult for shampoos and other aqueous products containing insecticide difficult to penetrate and lead to loss in efficacy. Aqueous lotions, shampoos and cream rinse also have too big a wetting angle for fluid to flow into the opercula directly. Because of these problems associated with various formulations, there has been an increasing evidence of development of resistance against these products.
Currently marketed Ovide® Lotion containing malathion, is the only insecticide, against which the lice has still not developed resistance. Since its introduction in the mid 1980's, there are no other commercial malathion preparations other than the lotion form. The pharmaceutical form of malathion contains 78% isopropyl alcohol, which functions as a solvent for delivery of malathion. A major difficulty encountered in applying this lotion is that it spreads freely on the scalp and hair shafts, thus giving false appearance of sufficient wetness after application of very small quantity (i.e., patients get the impression that this quantity is sufficient). Moreover, the lotion (due to its low viscosity) may easily run into the eyes, ears and down the patient's neck causing eye, ear and skin irritation as well as soiling the clothes. The patient is instructed to apply the lotion for 8-12 hours and not go near open flame or use a hair dryer during this time due to higher alcohol content which is flammable.
Treatment against ectoparasites further includes applying permethrin cream (5%), pyrethrin shampoo, lindane (1%) lotion, crotamiton cream, or oral dosage of ivermectin. Permethrin and lindane treatment requires applying the drugs from the neck down at night and washed off in the morning. Reapplication is often required. Many of these drugs are either toxic to nervous system or causes allergy. For example, lindane can not be used on infants, children, pregnant/nursing women, people with seizures or other neurological diseases. The National Pediculosis (head lice) Association recently established a database to track “adverse event” reports related to use of lindane to treat head lice in the U.S. In the first 24 months, more than 500 events were reported (County Sanitation Districts 2000). In 1996, in response to a petition from several public interest groups in the U.S., the Food and Drug Administration reviewed its regulations and determined that lindane should be used only as a “treatment of last resort” for lice and scabies. Lindane 1% shampoo is banned in California due to environmental problems with lindane in sewage effluent. Crotamiton cream has allergic activity. Oral dosage of ivermectin cannot to be used in infants or pregnant women. Antihistamines often are needed to relieve itching for the treatment.
Thus, there is a continuing need for a pharmaceutical formulation containing stable insecticides including organophosphate insecticides, such as malathion, that are effective, safe and have a short application time.